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Mortality Not Affected By Low-Dose Steroids in Severe Sepsis and Septic Shock: Presented at CCCF

By Pam Harrison

TORONTO, CANADA -- October 31, 2007 -- Low-dose steroids have virtually no effect on all-cause mortality when used in patients with severe sepsis and septic shock, according to results from the Corticosteroid Therapy of Septic Shock study (CORTICUS), a large-scale, randomised, placebo-controlled trial funded by the European Society of Intensive Care Medicine.

The study was presented by Charles Sprung, MD, Professor of Medicine, The Hebrew University of Jerusalem, Director, General Intensive Care Unit, Hadassah Hebrew University Medical Center, Department of Anaesthesiology and Critical Care Medicine, Hadassah University Hospital, Jerusalem, Israel.

The researchers analysed outcomes in 499 patients who were randomised to low-dose steroids (n = 215) or placebo (n = 248). Patients had clinical evidence of infection within 72 hours of enrolment in the study as well as any of the well-described inclusion criteria for sepsis trials. They also had systolic blood pressure <90 mm Hg or a >50 mm Hg decrease despite adequate fluid, or the need for vasopressors for at least 1 hour to maintain a systolic blood pressure at 90 mm Hg or greater.

The study medication was 50 mg hydrocortisone, given as an IV bolus four times daily for 5 days, then twice daily for the next 3 days, then as a single daily dose between days 9 and 11.

The source of infection involved everything from the lung, urinary tract and gastrointestinal tract, and soft tissue, as Dr. Sprung noted in a presentation on October 30. The adrenocorticotropic hormone (ACTH) stimulation test was used to separate patients into responders and nonresponders.

The primary endpoint of the study was all-cause mortality at 28 days.

At 28 days, 34.3% of patients receiving steroids had died compared with 31.5% of placebo controls, which was not significant. Responses according to ACTH test results were also not statistically different, with mortality rates of 39.2% for nonresponders and 36.1% for responders.

At 1 year, 56.6% of the steroid group had died as had 54% of placebo controls; again, not a significant difference between the two groups.

There was again no significant difference in rates of reversal of shock between steroid and placebo patients, but among patients in whom shock was reversed, "you could reverse shock sooner if patients received steroids than placebo," Dr. Sprung noted. Shock reversal occurred at a median of 3.3 days in steroid recipients and 5.8 days for placebo patients, a difference between the groups that was significant (P <.0001).

This difference in time to shock reversal also held true among both responders and nonresponders, where in both groups, shock was reversed sooner if patients were treated with steroids, he added. The steroid group also had less cardiovascular organ system dysfunction as reflected by their score on the Sequential Organ Failure Assessment (SOFA) compared with placebo.

Disturbingly, however, the incidence of superinfection was higher in the steroid group at 33.3% than in the placebo group, 26.3%, and there was slightly more new sepsis, new septic shock, and more repeat shock among steroid recipients than placebo patients.

In favour of steroids, their use was not associated with an increase in polyneuropathy.

Based on the CORTICUS results, the investigators suggested that IV hydrocortisone be given only to adult patients after blood pressure is identified to be poorly responsive to fluid resuscitation and vasopressor therapy.

They also recommended the ACTH simulation test not be used to identify a subset of adults with septic shock who should receive hydrocortisone therapy, and that oral fludrocortisone be considered optional if hydrocortisone is used.


[Presentation title: CORTICUS -- Steroids for Septic Shock RCT.]

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